Obesity is one of our nation's most serious health problems. The treatment of this disorder experienced a serious setback last year when two popular weight loss medications -- fenfluramine and dexfenfluramine -- were withdrawn from the market because of concerns that they were associated with valvular heart disease. Despite this unfortunate occurrence, it appears that pharmacotherapy will play an increasingly important role in the management of obesity in the next decade. In November 1997, the Food and Drug Administration approved sibutramine, a serotonin and norepinepherine re-uptake inhibitor, for "weight loss and maintenance of weight loss". Orlistat, a gastric and pancreatic lipase inhibitor, is now being considered for similar approval, with several other medications likely to follow. Previous studies indicate that optimal weight losses and improvements in health are likely to be obtained when behavioral and pharmacologic interventions are combined. Behavior therapy facilitates adherence to exercise and medication recommendations, whereas pharmacotherapy, by reducing hunger and increasing satiety, aids efforts to consume a reduced calorie diet. Long-term pharmacotherapy also holds promise of improving the maintenance of weight loss, a shortcoming of behavioral treatment. The proposed study will examine, in an 18-month trial, the separate and combined effects of behavior therapy and pharmacotherapy for obesity. A total of 296 obese men and women (BMI greater than 32 kg/m2) will be randomly assigned to one of four conditions: 1) Medication (i.e., sibutramine) Plus Standard Care; 2) Medication Plus Individual Behavior Modification (provided by a physician in brief visits); 3) Medication Plus Group Behavior Modification; or 4) Group Behavior Modification Alone. We predict that subjects treated by medication, combined with either individual or group behavior modification, will achieve significantly greater weight losses and improvements in health than those treated by Medication Plus Standard Care. This will result from the latter subjects' significantly better adherence to diet, exercise, and medication recommendations. We also predict that subjects treated by medication plus behavior modification (in individual or group sessions) will achieve significantly greater weight losses (particularly during the last 9 months) than persons who receive Group Behavior Modification Alone. If confirmed, the above findings will have important implications for treating obesity in primary care.